Harnessing the Power of IMGN529: Advancing B-Cell Lymphoma and Leukemia Treatment through Anti-CD37 Maytansinoid Conjugate Therapy

CD37 is a protein found on the surface of B-cells and is a potential target for cancer therapies due to its limited presence in healthy tissues. A range of anti-CD37 monoclonal antibodies was developed and assessed for their ability to bind to CD37, inhibit the growth of lymphoma cells, and induce cell death. The antibody K7153A was identified as the most effective, exhibiting superior direct activity and effector functions compared to other compounds, including TRU-016 and rituximab.

K7153A was then modified to create a humanized version, which was subsequently linked to the potent toxin DM1 to form the antibody-drug conjugate IMGN529. This conjugate maintained the high binding specificity and strong pro-apoptotic activity of K7153A, showing similar ADCC activity and comparable CDC against certain cell lines.

In vitro tests revealed that IMGN529 was significantly more cytotoxic against various NHL cell lines, with a lower effective concentration than K7153A alone. In animal models, IMGN529 demonstrated greater efficacy against SU-DHL-4 and BJAB tumors at lower doses than the antibody alone.

These findings suggest that IMGN529 effectively combines the anti-tumor properties of its antibody component with the cytotoxic payload, making it a promising candidate for treating CD37-positive lymphomas and leukemias. The study was presented at the 102nd Annual Meeting of the American Association for Cancer Research and published in Cancer Research.